We are submitting a proposal for a renewal of a K24 Mid-Career development Award to support the efforts of John N. van den Anker, M.D., Ph.D. Dr. van den Anker is a Board Certified Pediatrician who is also certified in Clinical Pharmacology; he is one of the only 30 pediatricians world-wide who has this dual certification and is one of the only two Neonatologists among them. Dr. van den Anker moved to Children's National Medical Center (CNMC) in 2002 to become Director of Pediatric Clinical Pharmacology, and he is currently Professor of Pediatrics, Pharmacology & Physiology at the George Washington University School of Medicine and Health Sciences (GWU). Significant institutional and departmental commitments, including financial support and an endowed Chair (Evan and Cindy Jones Professor of Pediatric Clinical Pharmacology) since 2005 have been provided to build a premier academic pediatric clinical research program. Dr. van den Anker is currently the P.I. of a number of external NIH grants in support of his pharmacological research. His expertise is in the area of developmental and neonatal pharmacology, primarily focusing on the effect of renal function on clinical pharmacokinetics of frequently used medicines in the neonate. His first K24 award (2004-2009) offered him the opportunity to gain skills in the general aspects of population pharmacokinetics and pharmacogenomics and to mentor 3-4 junior faculty members in pediatric pharmacology research. In this proposal, he plans to continue mentoring 3-4 junior faculty members who are conducting pharmacological studies in the areas of HIV/AIDS, psychiatry and anesthesiology. In addition, he will perform a research project that will focus on the development of a pharmacokinetic model for methadone dosing in neonates and young infants that will incorporate developmental changes (CYP2B6 activity and renal function) and pharmacogenetic information (CYP2B6 gene) relevant to methadone pharmacokinetics. The long-term goal of the proposed investigation is to improve the safe and effective use of methadone in neonates and young infants.